Two alternative mechanisms that regulate the presentation of apoptotic cell engulfment signal in Caenorhabditis elegans

Mol Biol Cell. 2007 Aug;18(8):3180-92. doi: 10.1091/mbc.e07-02-0138. Epub 2007 Jun 13.

Abstract

Phosphatidylserine exposed on the surface of apoptotic mammalian cells is considered an "eat-me" signal that attracts phagocytes. The generality of using phosphatidylserine as a clearance signal for apoptotic cells in animals and the regulation of this event remain uncertain. Using ectopically expressed mouse MFG-E8, a secreted phosphatidylserine-binding protein, we detected specific exposure of phosphatidylserine on the surface of apoptotic cells in Caenorhabditis elegans. Masking the surface phosphatidylserine inhibits apoptotic cell engulfment. CED-7, an ATP-binding cassette (ABC) transporter, is necessary for the efficient exposure of phosphatidylserine on apoptotic somatic cells, and for the recognition of these cells by phagocytic receptor CED-1. Alternatively, phosphatidylserine exposure on apoptotic germ cells is not CED-7 dependent, but instead requires phospholipid scramblase PLSC-1, a homologue of mammalian phospholipid scramblases. Moreover, deleting plsc-1 results in the accumulation of apoptotic germ cells but not apoptotic somatic cells. These observations suggest that phosphatidylserine might be recognized by CED-1 and act as a conserved eat-me signal from nematodes to mammals. Furthermore, the two different biochemical activities used in somatic cells (ABC transporter) and germ cells (phospholipid scramblase) suggest an increased complexity in the regulation of phosphatidylserine presentation in response to apoptotic signals in different tissues and during different developmental stages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / metabolism
  • Apoptosis*
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism
  • Embryonic Development
  • Germ Cells / cytology
  • Humans
  • Ligands
  • Membrane Proteins / metabolism
  • Mice
  • Milk Proteins / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Mutation / genetics
  • Phagocytosis*
  • Phosphatidylserines / metabolism
  • Phospholipid Transfer Proteins / chemistry
  • Phospholipid Transfer Proteins / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction*

Substances

  • ATP-Binding Cassette Transporters
  • Antigens, Surface
  • CED-7 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Ligands
  • Membrane Proteins
  • Mfge8 protein, mouse
  • Milk Proteins
  • Phosphatidylserines
  • Phospholipid Transfer Proteins
  • Recombinant Fusion Proteins
  • ced-1 protein, C elegans